Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
Célio Júnior da C Fernandes1, Rodrigo A Foganholi da Silva2,3, Patrícia F Wood1
1Laboratory of Bioassays and Cellular Dynamics, Department of Chemical and Biological Sciences, Institute of Biosciences, UNESP-São Paulo State University, Botucatu 18618-970, SP, Brazil.
Journal of Functional Biomaterials
|March 28, 2023
Summary
Titanium exposure epigenetically modifies endothelial cells, impacting bone healing. Histone deacetylase 6 (HDAC6) plays a key role, offering potential therapeutic targets for improving osseointegration and patient recovery.
Area of Science:
- Biomaterials Science
- Cell Biology
- Epigenetics
Background:
- Osseointegration of biomaterials is crucial for bone development and regeneration.
- Endothelial cells play a vital role in angiogenesis, a process essential for osseointegration.
- Understanding the epigenetic response of endothelial cells to biomaterials like titanium is critical.
Purpose of the Study:
- To investigate the epigenetic effects of titanium-enriched media on human umbilical vein endothelial cells (HUVECs).
- To identify key epigenetic players involved in the endothelial cell response to titanium during simulated osseointegration.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were exposed to titanium-enriched medium derived from incubated titanium discs.
- Molecular and epigenetic analyses were performed on harvested cells after 72 hours of exposure.
- Specific epigenetic enzymes, including Histone Deacetylases (HDACs), Sirtuin-1 (Sirt1), DNA Methyltransferases (DNMTs), and Ten-eleven Translocation (TET) methylcytosine dioxygenases, were assessed.
Main Results:
- Titanium exposure induced a significant repertoire of epigenetic modifications in endothelial cells.
- Histone deacetylases (HDACs) and NAD-dependent deacetylase sirtuin-1 (Sirt1) were identified as key players in regulating chromatin and DNA methylation.
- HDAC6 was highlighted as a critical mediator of titanium-induced epigenetic changes, potentially linked to cytoskeleton rearrangement.
- Sirt1 modulation was found to be relevant in response to reactive oxygen species (ROS) production.
Conclusions:
- Titanium dynamically influences the microenvironment, affecting endothelial cell performance through epigenetic modulation.
- HDAC6 is a significant factor in titanium-mediated epigenetic mechanisms within endothelial cells.
- The identified epigenetic enzymes are druggable, presenting opportunities for biotechnological interventions to enhance angiogenesis and accelerate bone growth for improved patient outcomes.
